回顾性观察研究：乙型肝炎病毒相关长期恩替卡韦治疗决心

StephenW

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        Medicine (Baltimore). 2016 Jan;95(4):e2614. doi: 10.1097/MD.0000000000002614.
Dynamics of Genotypic Mutations of the Hepatitis B Virus Associated With Long-Term Entecavir Treatment Determined With Ultradeep Pyrosequencing: A Retrospective Observational Study.Zhang XX1, Li MR, Cao Y, Zhang RW, Zhang Y, Li F, Xi HL, Xu XY.
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• 1From the Department of Infectious Disease, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, Beijing, China.
  

AbstractThe aim of the study is to explore the evolution of genotypic mutations within the reverse transcriptase region in partial virological responders (PVRs) receiving long-term entecavir (ETV) treatment.A total of 32 patients were classified as completely virological responders (CVRs) (n = 12) or PVRs (n = 20). Five partial responders were hepatitis B virus (HBV)-DNA positive after long-term therapy, which lasted for >3 years. A total of 71 serum samples from these 32 patients were assayed by ultra-deep pyrosequencing (UDPS): 32 samples were from all patients at baseline, and 39 were from PVRs with sequential inter-treatment.Approximately 84,708 sequences were generated per sample. At baseline, the quasispecies heterogeneity did not significantly differ between the 2 groups. The frequencies of substitutions indicating pre-existence of nucleos(t)ide analog resistant (NAr) mutants ranged from 0.10% to 6.70%, which did not statistically differ between groups either. However, the substitutions associated with the NAr mutants were significantly different from those associated with the non-NAr mutants in 13 patients; 6 of these patients were PVRs and the others were CVRs. Five patients were HBV DNA positive after regular ETV monotherapy for >3 years, and 4 of these patients underwent mild NAr substitution fluctuations (<20%). One patient developed virological breakthrough while bearing single, double, and triple (rtL180 M, rtM204 V, rtS202G) substitutions. In addition to the common substitutions, unknown amino acid substitutions, such as rtL145 M/S, rtF151Y/L, rtR153Q, rtI224 V, rtN248H, rtS223A, rtS256C, need to be further verified.NAr substitutions are observed at frequencies of 0.10% to 6.7% before therapy. Long-term ETV therapy generally results in virological responses, as long as the proportion of resistance mutations remains at a relatively low level. Genotypic resistance to ETV is detected in all PVRs receiving long-term ETV therapy.

StephenW

抽象

发给：
医学（巴尔的摩）。 2016年一月; 95（4）：e2614。 DOI：10.1097 / MD.0000000000002614。
回顾性观察研究：乙型肝炎病毒相关长期恩替卡韦治疗决心与超深焦磷酸测序的基因型突变的动态。
张XX1，李先生，曹Y，张RW，张勇，李楼曦HL，徐XY。
作者信息

    1从传染病，北京大学第一医院，8号西什库大街，西城区，中国北京部。

抽象

这项研究的目的是探讨基因型突变演化部分病毒学应答器（PVR）逆转录区域内长期接受恩替卡韦（ETV）treatment.A共32例为完全病毒学应答（对CVRs）（ N = 12）或个人录像机（N = 20）。五部分响应者乙型肝炎病毒（HBV）-DNA长期治疗后积极，持续时间> 3年。共有来自这32例患者71血清样品进行超深焦磷酸测序（UDPS）分析：32个样品分别来自所有患者在基线和39人来自个人录像机每个样品生成连续的跨treatment.Approximately 84708序列。基线时，准种异质性没有显著2组之间差异。表明核苷的前生替换的频率（T）IDE类似物具有抗性（NAR）突变体介于0.10％至6.70％，这并没有统计学上不同群体之间无论是。然而，与NAR突变体相关的取代是从在13个患者中的非NAR突变体相关的那些显著不同;这些患者中有6个人录像机和其他人对CVRs。五例患者HBV DNA阳性定期ETV单药治疗> 3年后，这些患者的4行温和NAR替代的波动（<20％）。一位患者制定病毒学突破，而轴承单人，双人和三（rtL180男，rtM204 V，rtS202G）替换。除了常见的取代，未知的氨基酸取代，如rtL145 M / S，rtF151Y / L rtR153Q，rtI224 V，rtN248H，rtS223A，rtS256C，需要进一步verified.NAr取代在0.10％频率观察治疗之前6.7％。长期ETV治疗通常导致病毒学反应，只要耐药突变的比例保持在一个较低的水平。在接受长期治疗ETV个人录像机的所有检测到ETV基因型耐药性。